This application describes four distinct but related investigations: 1) We propose to investigate the cellular regulation of the system of genes encoding the polypeptides of lactate dehydrogenase. The differential function of these genes generates the complex isozyme patterns characterizing the cell at each step in differentiation. Basic to this study is the purification and characterization of four isozymes from two species of fish. These are LDH-A4 and LDH-B4 and two alternate forms of LDH-C4. Amino acid composition, peptide profile, amino acid sequence, and enzymatic properties must be determined to correlate protein structure with function and with response to regulatory controls. Feedback control by gene products may determine the rate of gene transcription. This will be tested by injecting cells with gene products before the normal onset of gene function. 2) We propose to examine the genetic basis for quantitative differences in the synthesis of the LDH-A and B proteins in mouse cells. The inheritance of different levels of LDH gene activity will be subjected to conventional genetic analysis through three generations of crosses between inbred strains of mice. 3) Cell interactions during development will be studied in allophenic mice and rabbits. The roles of cell genotype and tissue environment will be examined in the differentiation of primoridal germ cells of female genotype within testes. Allophenic rabbits containing mouse cells will be used to test the limits of immunological tolerance as well as species specificity in cellular communication. 4) We propose to develop the required techniques and procedures for nuclear transplantation in mouse eggs.